Choline: yet another source of dietary mismatch?

And one that, yet again, disproportionately affects women

This article is sponsored by Needed, providing moms with unrivaled nutrition for fertility, pregnancy, and postpartum.

Sometimes my nerd-brain kicks into high-hear and I get really, really excited about going deep on some biological topic, and when Needed asked me to do some research on choline, it made me want to write a dissertation on the biochemical importance of this fascinating little molecule. Then I realized, I don’t have time, and neither do you, but I am going to get a tiny bit more technical than usual in this post. But stick with me! There’s an exciting twist at the end.

First of all, what is choline and why should we care about it? Choline is a vitamin-like essential nutrient that seems to defy conventional classification. It’s not a vitamin by strict definition, it’s not a hormone, but it’s a precursor for all kinds of super important molecular thingies in your body. Our bodies can synthesize choline in the liver, but not very well, so most animals rely on additional choline from their diet. We will get into choline and diet more at the end of this article, but for now I will briefly mention that meats, poultry and eggs are the richest sources of choline in the human diet. It’s also found in breastmilk and is frequently added to baby foods.

Choline’s role in the body is diverse and COMPLEX. In fact, a lot of the research on choline is brand-spanking-new and we don’t fully understand all of its functions and interactions. But we do know it’s super important. For instance, it’s a precursor for essential cell components, like the phospholipids that form cell membranes (the permeable little sacs that hold all of the inside-stuff inside the cell inside and keep the outside-stuff outside–unless the stuff is lipid-soluble or has the password). Choline-derived compounds, such as sphingomyelin, also help form “lipid rafts” that play a key role in intercellular signaling (like little cellular walkie-talkies), AND choline is a precursor for the neurotransmitter acetylcholine, which is the chief neurotransmitter of the parasympathetic nervous system. Neurotransmitters are how neurons (those spiny-looking cells in your brain) communicate with one another, and the parasympathetic nervous system is the part of the nervous system that contracts smooth muscles, dilates blood vessels, increases bodily secretions, slows heart rate, and is involved in stuff like neural development and memory formation. So you need choline in order for your neurons to talk to each other and in order for all of those wonderful parasympathetic nervous system functions to work.

But that’s not all! It turns out that choline is also involved in methyl donor metabolism, a process which helps modulate gene expression! It’s a precursor for the osmoregulator trimethylglycine (betaine), which plays a key role in epigenetic regulation. I used to work in a lab at Stanford studying epigenetics (I was the intern, which meant I mostly spent my time watching videos of fish and counting the number of times they did a mind-numbingly boring fish behavior), so I have a deep appreciation for the field. Epigenetics is this really cool area of research focused on how your behaviors and interactions with the environment alter your gene expression, by turning on and off sequences of DNA in your cells (and it is also one of the most talked-about and misunderstood areas of science these days). Anyway, choline plays a key role in epigenetic processes—such as methylation—key to helping support gene, protein, and cellular function.

But wait! There’s MORE! Choline is also a precursor to phosphatidylcholine, a major component of pulmonary surfactant which plays a role in the proper development of fetal lung tissue. AND it may also play a role in gut health and maintenance of the gut microbiome by helping with the intestinal absorption of lipids.

In other words, choline is involved in many key processes: from brain health to muscle function to healthy methylation to gut health. It’s kind of an important little thingamajig.

And it’s an especially important thingamajig for mothers and babies. Both pregnancy and lactation increase demand for choline dramatically. Choline is needed for building cellular membranes–including in both fetal and placental tissues, for healthy methylation processes (which helps to regulate maternal gene expression - think of all of those crazy changes the pregnant body goes through) and for transport and metabolism of lipoproteins (involved in distributing key molecules to maternal tissues and the fetus through the placenta).

Choline consumption during pregnancy and breastfeeding also supports healthy fetal brain development. Since humans experience the vast majority of brain growth starting in the last trimester of pregnancy and up to age five, demand for choline is high during this time . Indeed, research suggests that higher maternal intakes of choline support neurocognition/neurodevelopment in children, including sustained attention and processing speed (source and source). Fascinating.

In fact, choline was probably SO important in our evolutionary past that women’s bodies actually evolved to better synthesize it in response to rising estrogen levels (which is exactly what happens during pregnancy). Remember that humans can synthesize choline, in addition to getting it from our diet, and de novo synthesis of choline in the liver is typically insufficient for both sexes, but a little less so for women. Adult men need 550 milligrams per day of choline, while adult women only need 425 milligrams (since our bodies are better at synthesizing it), UNLESS we are pregnant or breastfeeding, in which case recommendations increase to 450-550 milligrams daily. So evolution ramped up choline production efficiency in women’s bodies just enough in order to compensate for the increased demand brought on by pregnancy and breastfeeding (which would have been the dominant female condition for most of our evolutionary past).

Fine, but are we getting enough?

Nope. We are not.

According to multiple rigorous research papers (like this one and this one), mean choline intakes for older children, men, women, and especially pregnant women are far below the recommended Adequate Intake (AI) levels in North America and other regions. According to at least one recent, large-scale study of 16,809 US residents over the age of 2, only 16% of men and 6% of women exceeded the adequate intake! Interestingly, 63% of 2- to 3-year-olds were meeting adequate intake, 45% of 4- to 8-year-olds, but then only 9% of 9- to 13-year-olds, 2% of 14–18 year olds and 7% of 19+ year olds!

The paper does not provide any explanations as to why there is so much variation according to age and sex. I suspect that children are meeting the choline requirement more easily simply because the AI is much lower for children (five-year-olds need less than half of what an adult male needs) and possibly because choline is often added to baby foods and formula. Additionally, choline is in high demand during lactation, and research suggests that adaptations during lactation increase choline supply. Additionally studies have shown that maternal choline intake supports breastmilk choline content to nourish the baby.

What surprised me most about these statistics, however, is that women are more often deficient, on average, than men, despite our ability to better synthesize choline thanks to estrogen. That indicates one thing: women are getting less choline than men from their diets. But why?

Another case of evolutionary mismatch?

I was unable to find any research on choline levels in hunter-gatherer populations. However, I strongly suspect that they would have had much higher levels than contemporary humans, based on dietary differences.

Does anyone wanna take a stab at guessing what food has the highest levels of choline per ounce? If you’ve read my other newsletter articles on dietary evolutionary mismatch, you might have a hunch.

It’s liver.

Specifically, beef liver (and I imagine any other large game liver). Honestly, sometimes I think I should just rename this newsletter “Eat Your Liver” based on everything I’ve learned about hunter-gatherer nutrition. I mean seriously, it’s a freaking SUPER food, and we are throwing it out or feeding it to the pets! Hunter-gatherers ate head to tail, and they definitely never let the organ meats go to waste. In fact, organ meats were a prized part of every kill, and the hunter would often save them for himself or his family.

But beef liver isn’t the only food with lots of choline. Beef liver has over 356 milligrams per 3-ounce serving, chicken liver 247 milligrams for the same size serving, and eggs have a whopping 294 milligrams per 3-ounce serving (about 2 eggs) which is GREAT NEWS for those of us who have a hard time with liver (me). In at least one study, egg consumption supported choline levels among study participants assigned to eat three eggs per day for four weeks (that’s a lot of eggs, especially when you consider the price spikes due to recent shortages). If you’re a vegan, or you don’t like eggs and liver, or you don’t have a spare $50/week to spend on eggs, you can eat soybeans and shitake mushrooms (but you might also want to take a supplement, because the levels are so much lower in these foods compared with eggs and liver).

But why are women more deficient?

Let’s circle back to why I think fewer women are meeting their adequate choline intake levels, even though they are lower for women than for men. According to research, women are more likely than men to avoid foods higher in fat and cholesterol due to dietary practice. Honestly, how many men do you know who order an egg-white-only omelet for breakfast?

But what might you miss out on when you avoid that egg-yolk (which tends to be higher in dietary fat and cholesterol)? Choline (along with vitamin A, D, E, K, B1, B2, B5, B6, B9, and B12). Liver has similarly been labeled as a high-cholesterol food, despite its superfood properties. Which brings me to the final twist in this article: Can foods higher in dietary cholesterol be part of a balanced diet?

It turns out that hunter-gatherers actually have very high cholesterol diets, and yet they have extremely low circulating levels of cholesterol. According to my academic hero, Melvin Konner, who was one of the first anthropologists to seriously study hunter-gatherer diets back in the 1980s, dietary cholesterol is not the cause of high cholesterol. On the contrary, for hunter-gatherers, the average serum total cholesterol is nearly always below 135 mg/dL, which is well within the healthy range (today’s healthy range is considered to be 125 to 200 mg/dL), DESPITE the fact that their diets were actually HIGHER in cholesterol than the typical contemporary American. This is due to the fact that hunter-gatherers ate quite a lot of meat, and while wild, grass-fed meat is leaner than most grain-fed meat we get at the supermarket, it is still quite high in cholesterol. Because of this, Konner proposed that dietary cholesterol may not be a major driver of cholesterol levels—a perspective that has gained traction among researchers over the past few decades. (If you want to go deeper on all of this, I highly recommend this paper).

So ladies, if you take away anything from this article, it’s that you should absolutely consider integrating healthy foods like egg yolks as part of a balanced diet, even if they have high cholesterol content! Do me a favor, especially if you are pregnant or breastfeeding, and EAT THOSE YOLKS.

And of course, it’s never a bad idea to take a high-quality supplement, just to cover your bases. Needed makes a good one :)

Final thoughts

As I mentioned at the outset, a lot of this is spanking new research. We don’t fully understand the role that choline plays in all bodily functions - man, it’s complex! - nor do we fully understand the consequences of lack of choline. What is clear is that adequate choline intake supports critical bodily functions, especially for mothers and babies: Everything from cellular metabolism, cell membrane structure and integrity, liver health, mood health, cognitive function, brain and central nervous system development, and neural tube formation. Although estrogen helps with synthesis, breastfeeding and post-menopausal women need as much as men, and women are more likely than men to be deficient throughout their adult lives.

So go out there and eat your liver (if you can stomach it), eat your egg yolks, and consider taking a quality supplement.

This article is sponsored by Needed, providing moms with unrivaled nutrition for fertility, pregnancy, and postpartum. For a 20% discount on their prenatal choline use code “ELENA” at checkout (valid for your first purchase – including both one-time purchases and already discounted subscriptions and plans).